I propose to study how genes which map in the major histocompatibility complex control the response and effector function of cytotoxic T lymphocytes. Cytotoxic T cells immunized against minor histocompatibility antigens of allogeneic cells, or against virus infected, or chemically modified syngeneic cells, or tumor specific antigens, can lyse only those target cells which share with the immunogen the minor antigen AND certain regions of the major histocompatibility complex. I will continue to study the cytotoxic response of mice to minor histocompatibility antigens. The cytotoxic cells will be generated by immunizations with allogeneic, H-2 identical cells and their specificity will be measured in short-term 51Cr-release assays. The specificity of the antibody response will also be studied. Using this system I will attempt to determine whether products of minor and major histocompatibility genes interact in the cytoplasm or at the cell surface to produce interaction antigens which are the target structures for T cells or whether the minor and major histocompatibility genes transmit their information independently to the cell surface. If the latter is correct, it will mean that the cytotoxic T cells have two recognition structures--one for the minor antigen, and another which interacts with self H-2 coded structures. It is hoped that these studies will contribute an understanding of the nature of the antigens which are immunogenic to T cells and on the nature of the T cell receptor itself. Transplantation techniques and the cytotoxic response offer the only way of studying the products of minor histocompatibility antigens at present. Any understanding gained in the response to minor histocompatibility antigens will almost certainly apply to the cytotoxic T cell response to all altered self membrane antigens.